We recently began seroepidemiological studies with the human T-cell leukemia virus (HTLV) in southern Japan, in the Caribbean region, and in AIDS patients, hemophiliacs, Haitians, and related controls. We identified a series of HTLV-related cell surface protein antigens (HTLV-MA) and conducted studies for antibody prevalence in various populations using tests for both HTLV-MA and various virion peptides. Such antibodies were found in essentially all cases of Japanese adult T-cell leukemia, in 16% of the healthy adults in Kyushu, and in 5-15% of the healthy Caribbeans. The same antibodies were found in 30-80% of the patients with AIDS and in 10-25% of the healthy hemophiliacs but not in more than 1-2% of matched healthy gay controls. We now propose to expand these studies to study the possibility that a virus in the HTLV family may be etiologically involved in AIDS. As a result of our recent studies, as well as those in the Gallo lab, HTLV is generally considered by most investigators as the leading candidate agent to cause AIDS. In the current proposal, we plan to expand our studies on this issue to evaluate the seroepidemiologic responses to HTLV-MA, gp61, p24, p29, and p95. Emphasis will be given to prospective studies and to various high-risk and control groups including lymphadenopathy cases (LAS) in gay men, various immunodeficiency states, hemophiliacs, infants with AIDS-like syndromes, Haitians, IV drug abusers, male and female sexual contacts of cases, AIDS cases of African and European origin, patients with severe infectious diseases in southern Japan and the Caribbean, and blood donors associated with AIDS cases where the only risk factor was blood transfusion. Additionally, we will try to isolate HTLV-like viruses from AIDS cases and related high risk groups, especially from antibody-negative cases. The spectrum of protein antigens that react with the different human sera will also be compared according to the class and origin of the HTLV-like agent and according to the class of antigen (virion encoded vs. virus activated cell encoded) that is detected.